B lymphocyte functional heterogeneity and activation requirements have been studied by a variety of coordinated approaches. New markers characterizing various mouse B cell subsets have been identified by the use of monoclonal antibodies and the functional properties of cells bearing these markers are being elucidated. Early events in B cell activation are being studied by the use of highly purified populations of defined B lymphocytes grown in both serum free and conventional medium. Techniques to grow long term lines of non-transformed human and mouse B lymphocytes, and for the cloning of human B cells have been developed. A molecular genetic approach to the characterization of genes which determine the differentiated state of given lymphocyte classes is now being developed. These approaches used together with the resources provided by mice with a B cell defect determined by the xid gene have provided an overall strategy to elucidate key elements in the biology of B lymphocytes.